Viral and Fungal Therapy

General Principles of Virology and Viral Pathogenesis

  • Method of Viral Transmission: Viruses can be transmitted through various pathways, including:     * Infected secretions.     * Ingestion of contaminated food or water.     * Breaks in the skin or mucous membranes.     * Sexual contact.     * Pregnancy and breast-feeding.     * Organ transplantation.
  • Mechanisms of Viral Infection: Viruses are classified as intracellular parasites.     * Entry: They gain entry into human hosts by binding to specific receptors located on cell membranes.     * Resistance: If a host lacks the specific receptors for a particular virus, that host is inherently resistant.     * Survival and Replication: Once inside the host cells, viruses hijack cellular metabolic activities for their own survival and replication.     * Dissemination: After new viruses are formed, they are released from the infected cell into the blood and surrounding tissues, leading to the transmission of the viral infection to other host cells.
  • Varying Infection States: Viral infections manifest in different ways:     * Mild, Localized Disease: Infections with few symptoms, such as the common cold.     * Severe Systemic Illness: Life-threatening conditions like HIV and Hepatitis.     * Outcome: Infections may ultimately lead to death.

Clinical Manifestations and Specific Viral Infections

  • Indicated Immune Response: Viruses induce both antibodies and immunity within the host.
  • Symptomatology:     * Infections may occur without any signs or symptoms of illness.     * Symptomatic Presentations: Typically include fever, headache, cough, malaise, nausea/vomiting (N/V), muscle pain, diarrhea, insomnia, and photophobia.     * Laboratory Findings: White Blood Cell (WBC) counts usually remain normal.     * Variability: Signs and symptoms vary significantly based on the specific virus and the tissues involved.
  • Examples of Viral Infections:     * Avian Flu (H5N1): A subtype of influenza A that can cause respiratory failure.     * COVID-19: Causative agent of the global pandemic.     * Herpesvirus Infections:         * Cytomegalovirus (CMV): Often asymptomatic in immunocompetent adults but acts as an opportunistic infection. It can transmit to the fetus in pregnant women, potentially causing learning disabilities and cognitive deficits. Active infection may involve cellular necrosis, pneumonitis, hepatitis, encephalitis, ulcers, and retinitis.         * Herpes Simplex Virus (HSV): Includes HSV 1 (cold sores) and HSV 2 (genital herpes). It can be passed to neonates during delivery, causing irritability, lethargy, jaundice, blood clotting issues, respiratory distress, seizures, coma, and death.         * Herpes Zoster (VZV): Responsible for Chicken pox and Shingles.     * HIV: Binds specifically to receptors on CD4+CD4+ cells, especially T lymphocytes. Initial symptoms are flu-like; these subside until the viral load becomes large enough to allow for opportunistic infections.     * HPV: A sexually transmitted disease (STD) that causes genital warts and several types of cancer.     * RSV (Respiratory Syncytial Virus): A common respiratory virus.     * Hepatitis:         * Hepatitis A: Transmitted via the fecal-oral route; presents with flu-like symptoms and jaundice. Most patients recover without issue.         * Hepatitis B: Transmitted through blood and body fluids; can lead to cirrhosis, liver cancer, liver failure, and death.         * Hepatitis C: Transmitted similarly to Hepatitis B (blood and body fluids).

Preventive and General Antiviral Considerations

  • Vaccines for Prevention:     * Purpose: To produce active immunity before exposure occurs.     * Function: Control epidemics of viral disease within a community.     * Targeted Diseases: Cervical cancer, chickenpox, measles, Hepatitis A and B, herpes zoster, mumps, poliomyelitis, rubella, smallpox, yellow fever, Rabies, and Influenza A, B, and Avian A.
  • Medications for Treatment:     * Medications inhibit viral reproduction but do not eliminate viruses fully from the tissues.     * General Characteristics: These drugs are often expensive, relatively toxic, and have limited efficacy.     * Primary Clinical Uses: Herpesvirus, HIV (antiretrovirals), Influenza, RSV, and Viral hepatitis infections.

Pharmacotherapy for COVID-19

  • Remdesivir:     * Route: Intravenous (IV).     * Pharmacokinetics: Highly protein bound with a half-life of 1 hour1\,hour; eliminated in urine and feces.     * Action: Inhibits viral DNA replication.     * Usage: Indicated for individuals 1212 years and older whose COVID-19 infection is at risk of progressing to severe infection.     * Adverse Effects: Severe bradycardia and hypersensitivity reactions (e.g., angioedema, wheezing).     * Nursing Implications: Must be administered only with Normal Saline (NS). Monitor the IV site carefully.
  • Other Medications: include tocilizumab (blocks inflammation) and baricitinib.

Antiviral Drugs for Herpes and Varicella-Zoster

  • Therapeutic Goals: Decreased duration of lesions, reduced itching, and reduced pain.
  • General Management: Use cautiously in patients with renal failure. Teach patients to stay well-hydrated.
  • Acyclovir (Prototype):     * Routes: PO (Oral), IV.     * Pharmacokinetics: Absorbed slowly and incompletely (15%−30%15\%-30\%). It is metabolized inside the viral cell, and the remainder is excreted unchanged in the urine.     * Action: Converted to acyclovir triphosphate, which inhibits viral DNA replication.     * Use: Herpes infections (cold sores and genital warts), Zoster (chicken pox and shingles).     * Adverse Effects: PO involves N/V, headache, malaise, and diarrhea. IV may rarely cause encephalopathy.     * Nursing Implications: Educate the patient that the medication is not a cure.
  • Drugs for Cytomegalovirus (CMV):     * Ganciclovir (Prototype): Given mostly IV because only 7%7\% is absorbed orally. Excreted mostly unchanged in urine. Inhibits viral DNA synthesis.         * Uses: Prevention of CMV in immunocompromised patients, transplant recipients, and HIV patients.         * Adverse Effects: Fever, chills, N/V, bone marrow suppression, neuropathy, retinal detachment, sepsis, and increased BUN/Creatinine.         * Nursing Implications: Monitor laboratory values including BUN, creatinine, CBC, and platelets.     * Other Drugs for CMV: cidofovir, foscarnet, and valganciclovir.
  • Additional Herpes/Varicella Drugs:     * docosanol: Topical application.     * famciclovir: PO; requires monitoring of CBC for blood dyscrasias.     * penciclovir: Topical application.     * valacyclovir: PO application.     * Trifluridine: Ophthalmic application.

Antiviral Drugs for RSV, Influenza, and Hepatitis

  • Respiratory Syncytial Virus (RSV):     * Goal: Improved respiratory status.     * Considerations: Risk of exposure during pregnancy (teratogenic).     * Treatment: ribavirin, INH.         * Ribavirin Pharmacokinetics: Metabolized at the cellular level; excreted in urine and feces. Inhibits replication.         * Ribavirin Adverse Effects: Fatigue, insomnia, nausea; less than 1%1\% experience cardiac arrest; decreased respiratory function.     * palivizumab: A monoclonal antibody that inhibits viral replication; used for premature infants (premies).
  • Influenza:     * Goal: Decrease flu-like symptoms (fever, malaise, pain, cough, rhinitis).     * Precautions: Use cautiously in the elderly and renal failure patients.     * amantadine hydrochloride: Monitor for side effects including depression, dizziness, nervousness, peripheral edema, and orthostatic hypotension.     * oseltamivir phosphate: A neuraminidase inhibitor; side effects include N/V and diarrhea.
  • Hepatitis B:     * Goal: Decrease malaise, myalgia, loss of appetite, abdominal pain, and jaundice.     * Treatment: lamivudine. Watch for serious drug interactions (hepatotoxicity).     * Adverse Effects: Pancreatitis (main), lactic acidosis, and hepatomegaly.
  • Hepatitis C:     * Goal: Decrease the chronicity of Hepatitis C.     * Treatment: Sofosbuvir. Inhibits viral replication.     * Combinations: Used with ribavirin or peginterferon alfa.     * Adverse Effects: Fatigue, headache, insomnia, chills, and anemia.

Antiretroviral Therapy (ART) for HIV

  • General Management:     * Goal: Reducing HIV-related morbidity and mortality.     * Adherence: Strict adherence is mandatory for viral suppression.     * Standard of Care: Combination ART is the gold standard. Watch for serious drug interactions.
  • Classifications and Actions:     * Nucleoside Reverse Transcriptase Inhibitors (NRTIs): Terminates viral replication. Prototype: zidovudine. Others include: abacavir, didanosine, dolutegravir, emtricitabine, lamivudine, stavudine, and tenofovir.     * Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs): Inhibits viral replication. Prototype: efavirenz. Others include: delavirdine, etravirine, nevirapine, and rilpivrine.     * Protease Inhibitors: Prevents poly-proteins needed for viral maturation. Prototype: saquinavir. Others include: atazanavir, darunavir, fosamprenavir, indinavir, lopinavir, nelfinavir, ritonavir, and tipranavir.     * Integrase Strand Transfer Inhibitors: Raltegravir.     * Fusion Protein Inhibitors: Enfuvirtide.     * CCR5 Antagonists: Maraviroc.     * Combination Medications: Bictegravir, emtricitabine, and tenofovir alafenamide.

Physiology and Pathophysiology of Fungal Infections

  • Fungal Classification:     * Groups: Yeasts and Molds.     * Dimorphic Fungi: Grow as yeasts at one temperature and molds at another.     * Dermatophytes: Grow specifically at core body temperature.     * Superficial Mycoses: Grow at the cutaneous level of the body.     * Disease Production: Fungi only produce disease in humans if they can grow at human body temperature.
  • Opportunistic Fungal Infections:     * Aspergillosis: Found in soil, water, and decaying vegetation.     * Candidiasis: Yeast-like fungus naturally present in the mouth, skin, intestinal tract, and vagina.     * Cryptococcosis: The most serious fungal infection for immunocompromised patients.     * Mucormycosis (Zygomycosis): Fungal infection of the sinuses, brain, or lungs caused by Mucor or Rhizopus.
  • Non-opportunistic Fungal Infections:     * Blastomycosis: Chronic infection with granulomatous/suppurative lesions; caused by inhaling Blastomyces dermatitidis.     * Coccidioidomycosis: Primarily a disease of the lungs.     * Dermatophytic Infections: Commonly referred to as tinea or ringworm; affects skin sites.     * Histoplasmosis: Affects lungs or other organs via dissemination.

Pharmacology of Antifungal Agents

  • Antifungal Prototypes:     * Polyenes: amphotericin B.     * Azoles: fluconazole.     * Echinocandins: caspofungin (used for candida and aspergillus).     * Pyrimidine Analog: flucytosine (used for cryptococcosis, candidiasis, and chromomycosis).     * Miscellaneous: griseofulvin (used for tinea).
  • Amphotericin B:     * Routes: IV, PO topical.     * Action: Binds to sterols in fungal cell membranes, increasing permeability, leading to cell leakage and death. May also damage host cells.     * Use: Systemic fungal or protozoan infections.     * Adverse Effects: Electrolyte abnormalities, anemia, nephrotoxicity, headache, chills, hypotension, N/V (worse with IV).     * Nursing Implications: Monitor for signs and symptoms of nephrotoxicity.     * Related Drug: Nystatin.
  • Azoles (Fluconazole):     * Routes: PO, IV.     * Pharmacokinetics: Metabolized by CYP 450; excreted in the urine.     * Action: Binds to sterols in fungal cell membranes to increase permeability and cause cell death.     * Use: Candida, cryptococcal meningitis in AIDS, prophylaxis for bone marrow transplantation.     * Adverse Effects: Diarrhea, N/V, headache, dizziness.     * Nursing Implications: Monitor liver studies; may cause elevation.     * Other Azoles: clotrimazole, itraconazole, ketoconazole, posaconazole, and voriconazole.